RESUMEN

Ulcerative colitis has been associated with psychological distress and an aberrant immune response. The immunomodulatory role of systemic cytokines produced during experimental intestinal inflammation in tonic immobility (TI) defensive behavior remains unknown. The present study characterized the TI defensive behavior of guinea pigs subjected to colitis induction at the acute stage and after recovery from intestinal mucosa injury. Moreover, we investigated whether inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-8, IL-10, and prostaglandins) act on the mesencephalic nucleus, periaqueductal gray matter (PAG). Colitis was induced in guinea pigs by intrarectal administration of acetic acid. The TI defensive behavior, histology, cytokine production, and expression of c-FOS, IBA-1, and cyclooxygenase (COX)-2 in PAG were evaluated. Colitis reduced the duration of TI episodes from the first day, persisting throughout the 7-day experimental period. Neuronal c-FOS immunoreactivity was augmented in both columns of the PAG (ventrolateral (vlPAG) and dorsal), but there were no changes in IBA-1 expression. Dexamethasone, infliximab, and parecoxib treatments increased the duration of TI episodes, suggesting a modulatory role of peripheral inflammatory mediators in this behavior. Immunoneutralization of TNF-α, IL-1ß, and IL-8 in the vlPAG reversed all effects produced by colitis. In contrast, IL-10 neutralization further reduced the duration of TI episodes. Our results reveal that peripherally produced inflammatory mediators during colitis may modulate neuronal functioning in mesencephalic structures such as vlPAG.

Asunto(s)

Colitis , Animales , Masculino , Cobayas , Colitis/metabolismo , Colitis/inducido químicamente , Colitis/inmunología , Pérdida de Tono Postural , Sustancia Gris Periacueductal/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Citocinas/metabolismo , Dexametasona/farmacología , Ciclooxigenasa 2/metabolismo , Infliximab/farmacología , Infliximab/uso terapéutico , Modelos Animales de Enfermedad

RESUMEN

Seizures are neurological disorders triggered by an imbalance in the activity of excitatory and inhibitory neurotransmitters in the brain. When triggered chronically, this imbalance can lead to epilepsy. Critically, many of the affected individuals are refractory to treatment. Given this, anti-inflammatory drugs, in particular glucocorticoids, have been considered as a potential antiepileptogenic therapy. Glucocorticoids are currently used in the treatment of refractory patients, although there have been contradictory results in terms of their use in association with antiepileptic drugs, which reinforces the need for a more thorough investigation of their effects. In this context, the present study evaluated the effects of dexamethasone (DEX, 0.6 mg/kg) on the electroencephalographic (EEG) and histopathological parameters of male Wistar rats submitted to acute seizure induced by pentylenetetrazol (PTZ). The EEG monitoring revealed that DEX reduced the total brainwave power, in comparison with PTZ, in 12 h after the convulsive episode, exerting this effect in up to 36 h (p < 0.05 for all comparisons). An increase in the accommodation of the oscillations of the delta, alpha, and gamma frequencies was also observed from the first 12 h onwards, with the accommodation of the theta frequency occurring after 36 h, and that of the beta frequency 24 h after the seizure. The histopathological analyses showed that the CA3 region and hilum of the hippocampus suffered cell loss after the PTZ-induced seizure (control vs. PTZ, p < 0.05), although DEX was not able to protect these regions against cell death (PTZ vs. DEX + PTZ, p > 0.05). While DEX did not reverse the cell damage caused by PTZ, the data indicate that DEX has beneficial properties in the EEG analysis, which makes it a promising candidate for the attenuation of the epileptiform wave patterns that can precipitate refractory seizures.

Asunto(s)

Ondas Encefálicas , Dexametasona , Electroencefalografía , Pentilenotetrazol , Ratas Wistar , Convulsiones , Animales , Dexametasona/farmacología , Dexametasona/efectos adversos , Pentilenotetrazol/toxicidad , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Convulsiones/fisiopatología , Masculino , Ratas , Ondas Encefálicas/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/fisiopatología , Anticonvulsivantes/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/fisiopatología

RESUMEN

Chronic and excessive glucocorticoid (GC) exposure can cause Cushing's syndrome, resulting in fat accumulation in selected body areas. Particularly in the brown adipose tissue (BAT), GC acts negatively, resulting in whitening of the tissue. We hypothesized that dysregulation of microRNAs by GC could be an additional mechanism to explain its negative actions in BAT. Male Wistar rats were divided into two groups: (1) Control sham and (2) GC group that was administered dexamethasone 6.25 mg/200 µL via osmotic pump implantation over 28 days. After this period, the animals were euthanized and BAT tissue was properly stored. Human fat cells treated with dexamethasone were used to translate the experimental results found in animals to human biology. GC-treated rat BAT presented with large lipid droplets, severely impaired thermogenic activation, and reduced glucose uptake measured by 18F-FDG PET/CT. GC exposure induced a reduction in the mitochondrial OXPHOS system and oxygen consumption. MicroRNA profiling of BAT revealed five top-regulated microRNAs and among them miR-21-5p was the most significantly upregulated in GC-treated rats compared to the control group. Although upregulation of miR-21-5p in the tissue, differentiated primary brown adipocytes from GC-treated rats had decreased miR-21-5p levels compared to the control group. To translate these results to the clinic, human brown adipocytes were treated with dexamethasone and miR-21-5p inhibitor. In human brown cells, inhibition of miR-21-5p increased brown adipocyte differentiation and prevented GC-induced glucose uptake, resulting in a lower glycolysis rate. In conclusion, high-dose GC therapy significantly impacts brown adipose tissue function, with a notable association between glucose uptake and miR-21-5p.

Asunto(s)

Adipocitos Marrones , Tejido Adiposo Pardo , Dexametasona , Glucocorticoides , MicroARNs , Ratas Wistar , Termogénesis , Animales , Humanos , Adipocitos Marrones/efectos de los fármacos , Adipocitos Marrones/metabolismo , Glucocorticoides/farmacología , MicroARNs/metabolismo , MicroARNs/genética , Masculino , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Dexametasona/farmacología , Termogénesis/efectos de los fármacos , Ratas , Glucosa/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fosforilación Oxidativa/efectos de los fármacos

RESUMEN

The aim of the study was to assess glucocorticoid sensitivity in survivors of childhood acute lymphoblastic leukemia using in vivo and in vitro tests. Thirty leukemia survivors of both sexes aged ≥18 years participated in the study and at least two years after therapy withdrawal. In vivo tests comprised: a) a very low dose intravenous dexamethasone suppression test for measurement of serum cortisol before, after, and % suppression, compared with 32 age-matched controls; and b) 0.25 mg overnight oral dexamethasone suppression test for assessment of salivary cortisol before, after, and % suppression. In vitro methods comprised: c) glucocorticoid receptor polymorphisms: BcI1-NR3C1 and A3669G; and d) splicing variant of glucocorticoid receptor GR-α mRNA by real-time quantitative polymerase chain reaction, compared with 32 controls. There was a reduction in salivary cortisol, and 73.3% of leukemia survivors showed high sensitivity according to % suppression after oral dexamethasone (p<0.05). Serum cortisol at baseline, after the test, % suppression after intravenous dexamethasone, and the percentage of high sensitivity were reduced in the leukemia group (%F=36.7; p<0.05). The BcI1-NR3C1 and A3669G polymorphisms were present in 11/30 (36.7%) and 5/30 (16.7%) patients, respectively. GR-α mRNA levels were lower in the leukemia group than in the controls (p<0.05). Survivors of acute lymphoblastic leukemia presented with reduced glucocorticoid sensitivity. Glucocorticoid sensitivity allows individualized treatment to avoid adverse effects and may be involved in cardiovascular disease risk among this particular group of cancer survivors.

Asunto(s)

Dexametasona , Glucocorticoides , Hidrocortisona , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Glucocorticoides , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Masculino , Femenino , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Hidrocortisona/sangre , Adolescente , Dexametasona/administración & dosificación , Dexametasona/farmacología , Niño , Adulto , Adulto Joven , Estudios de Casos y Controles , Saliva/química , Saliva/metabolismo , Supervivientes de Cáncer , Sobrevivientes , Polimorfismo de Nucleótido Simple

RESUMEN

The objective of the study was to evaluate the effect of photobiomodulation (PBM) with laser on the inflammatory process in an experimental in vitro model of ACO. The groups were: (1) human bronchial epithelial cells (BEAS-2B); (2) BEAS-2B cells treated with dexamethasone; (3) BEAS-2B cells irradiated with laser; (4) BEAS-2B cells stimulated with cigarette smoke extract (CSE) + House Dust Mite (HDM); (5) BEAS-2B cells stimulated with CSE + HDM and treated with dexamethasone; (6) BEAS-2B cells incubated with CSE + HDM and irradiated with laser. After 24 h, cytokines were quantified. There was a reduction in TNF-α, IL-1ß, IL-6, IL-4, IL-5, IL-13, IL-17, IL-21, IL-23, and an increase in IL-10 and IFN-γ in cells from the laser-irradiated ACO group compared to only ACO group. With these results, we can suggest that photobiomodulation acts in the modulation of inflammation observed in ACO, and may be a treatment option.

Asunto(s)

Asma , Citocinas , Terapia por Luz de Baja Intensidad , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Asma/radioterapia , Enfermedad Pulmonar Obstructiva Crónica/radioterapia , Citocinas/metabolismo , Animales , Línea Celular , Modelos Biológicos , Pyroglyphidae/inmunología , Células Epiteliales/efectos de la radiación , Dexametasona/farmacología , Humo/efectos adversos

RESUMEN

OBJECTIVE: To investigate the effects of Araucaria sp. brown propolis (ABP) against trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. METHODS: Animals received vehicle (1% DMSO, 1 ml/kg) or hydroalcoholic extract of ABP (hydroalcoholic extract of Araucaria sp. brown propolis (HEABP), 30, 100, and 300 mg/kg) orally, or dexamethasone (25 mg/kg, s.c.) for 5 days. On day 4, the animals received intracolonic TNBS (150 mg/kg), on day 6 they were euthanized. The weight of the animals, the macroscopic and microscopic colonic damage, reduced glutathione (GSH) and malondialdehyde (MDA) levels, and the activity of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in colon homogenate. The action of HEABP and two isolated compounds in neutrophil migration was recorded. KEY FINDINGS: HEABP (100 and 300 mg/kg), but not dexamethasone, decreased colonic lesion, and increased colonic mucin staining. In parallel, HEABP decreased MDA and restored GSH levels and the activity of SOD, CAT, and GST in the colon. A dose-dependent inhibition of MPO activity was observed (LogIC50 = 1.9). Moreover, HEBPA and the junicedric and abietic acids inhibited the neutrophil chemotaxis in vitro and HEBPA reduced neutrophil migration in vivo. CONCLUSION: HEABP may be promising in the therapies for inflammatory bowel diseases, reducing oxidative and inflammatory damage, especially mediated by neutrophils.

Asunto(s)

Colitis Ulcerosa , Malondialdehído , Estrés Oxidativo , Extractos Vegetales , Própolis , Ratas Wistar , Ácido Trinitrobencenosulfónico , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Colitis Ulcerosa/metabolismo , Própolis/farmacología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Extractos Vegetales/farmacología , Malondialdehído/metabolismo , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo , Peroxidasa/metabolismo , Glutatión/metabolismo , Superóxido Dismutasa/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Modelos Animales de Enfermedad , Dexametasona/farmacología , Tracheophyta/química , Catalasa/metabolismo , Relación Dosis-Respuesta a Droga , Antioxidantes/farmacología , Glutatión Transferasa/metabolismo

RESUMEN

OBJECTIVE: To compare the effect of submucosal cryotherapy using cold saline to dexamethasone sodium phosphate and diclofenac sodium injections on substance P and interleukin 6 release in experimentally induced pulpal inflammation in rabbits' molar teeth. METHODOLOGY: Fifteen rabbits were randomly classified into 3 groups according to the submucosal injection given: cold saline, dexamethasone sodium phosphate, and diclofenac sodium. A split-mouth design was adopted, the right mandibular molars were experimental, and the left molars served as the control without injections. Intentional pulp exposures were created and left for 6 hours to induce pulpitis. Pulpal tissue was extracted and examined for SP and IL-6 levels using ELISA. Within each group, the level of cytokines released was measured for both control and experimental groups for intragroup comparison to determine the effect of injection. The percentage reduction of each mediator was calculated compared with the control side for intergroup comparison then the correlation between SP and IL-6 levels was analyzed using Spearman's rank order correlation coefficient. Statistical analysis was performed, and the significance level was set at p<0.05. RESULTS: Submucosal cryotherapy, dexamethasone sodium phosphate, and diclofenac sodium significantly reduced SP and IL-6 pulpal release. Submucosal cryotherapy significantly reduced SP more than and IL-6 more than dexamethasone sodium phosphate and diclofenac sodium. Pulpal reduction of SP and IL-6 showed a strong positive significant correlation. CONCLUSIONS: Submucosal cryotherapy reduces the pulpal release of SP and IL-6 and could be tested as an alternative to premedication to potentiate the effect of anesthesia and control postoperative endodontic pain.

Asunto(s)

Antiinflamatorios no Esteroideos , Crioterapia , Pulpa Dental , Dexametasona , Diclofenaco , Ensayo de Inmunoadsorción Enzimática , Interleucina-6 , Pulpitis , Distribución Aleatoria , Sustancia P , Animales , Conejos , Pulpitis/terapia , Diclofenaco/farmacología , Dexametasona/farmacología , Dexametasona/análogos & derivados , Interleucina-6/análisis , Crioterapia/métodos , Sustancia P/análisis , Antiinflamatorios no Esteroideos/farmacología , Pulpa Dental/efectos de los fármacos , Factores de Tiempo , Reproducibilidad de los Resultados , Resultado del Tratamiento , Masculino , Estadísticas no Paramétricas , Modelos Animales de Enfermedad , Antiinflamatorios/farmacología , Solución Salina , Valores de Referencia

RESUMEN

Natural products have been used to treat inflammatory reactions and led to the discovery of new anti-inflammatory drugs. Geopropolis (GEO) is produced by stingless bees and has been used by indigenous people to improve the immune functions. Here, a possible synergism between GEO and dexamethasone (DEX) was assessed on human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS). PBMC viability was evaluated by the MTT, apoptosis/necrosis by flow cytometry, cytokine and eicosanoids production by ELISA, and intracellular pathways by polymerase chain reaction. GEO and DEX alone or in combination did not affect cell viability. GEO in combination with lower concentrations of DEX inhibited cytokine production (TNF-α, IL-1ß, and IL-10). No effects were seen on eicosanoids nor in intracellular pathways. Despite not always being more efficient than the isolated treatments, GEO + DEX seemed to be promising and allow the use of DEX in lower concentrations, reducing adverse effects.

Asunto(s)

Antiinflamatorios , Dexametasona , Leucocitos Mononucleares , Lipopolisacáridos , Própolis , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Abejas , Antiinflamatorios/farmacología , Animales , Dexametasona/farmacología , Lipopolisacáridos/farmacología , Própolis/farmacología , Células Cultivadas , Citocinas/metabolismo , Supervivencia Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Sinergismo Farmacológico

RESUMEN

BACKGROUND: Cytokine storm and oxidative stress are present in chronic obstructive pulmonary disease (COPD). Individuals with COPD present high levels of NF-κB-associated cytokines and pro-oxidant agents as well as low levels of Nrf2-associated antioxidants. This condition creates a steroid-resistant inflammatory microenvironment. Lacticaseibacillus rhamnosus (Lr) is a known anti-cytokine in lung diseases; however, the effect of Lr on lung inflammation and oxidative stress in steroid-resistant COPD mice remains unknown. OBJECTIVE: Thus, we investigated the Lr effect on lung inflammation and oxidative stress in mice and macrophages exposed to cigarette smoke extract (CSE) and unresponsive to steroids. METHODS: Mice and macrophages received dexamethasone or GLPG-094 (a GPR43 inhibitor), and only the macrophages received butyrate (but), all treatments being given before CSE. Lung inflammation was evaluated from the leukocyte population, airway remodeling, cytokines, and NF-κB. Oxidative stress disturbance was measured from ROS, 8-isoprostane, NADPH oxidase, TBARS, SOD, catalase, HO-1, and Nrf2. RESULTS: Lr attenuated cellularity, mucus, collagen, cytokines, ROS, 8-isoprostane, NADPH oxidase, and TBARS. Otherwise, SOD, catalase, HO-1, and Nrf2 were upregulated in Lr-treated COPD mice. Anti-cytokine and antioxidant effects of butyrate also occurred in CSE-exposed macrophages. GLPG-094 rendered Lr and butyrate less effective. CONCLUSIONS: Lr attenuates lung inflammation and oxidative stress in COPD mice, suggesting the presence of a GPR43 receptor-dependent mechanism also found in macrophages.

Asunto(s)

Lacticaseibacillus rhamnosus , Macrófagos , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica , Receptores Acoplados a Proteínas G , Animales , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Estrés Oxidativo/efectos de los fármacos , Receptores Acoplados a Proteínas G/metabolismo , Ratones , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Humo/efectos adversos , Dexametasona/farmacología , Butiratos/farmacología , Pulmón/efectos de los fármacos , Pulmón/metabolismo

RESUMEN

Current and thorough information on the ecotoxicological consequences of pharmaceuticals is accessible globally. However, there remains a substantial gap in knowledge concerning the potentially toxic effects of COVID-19 used drugs, individually and combined, on aquatic organisms. Given the factors above, our investigation assumes pivotal importance in elucidating whether or not paracetamol, dexamethasone, metformin, and their tertiary mixtures might prompt histological impairment, oxidative stress, and apoptosis in the liver of zebrafish. The findings indicated that all treatments, except paracetamol, augmented the antioxidant activity of superoxide dismutase (SOD) and catalase (CAD), along with elevating the levels of oxidative biomarkers such as lipid peroxidation (LPX), hydroperoxides (HPC), and protein carbonyl content (PCC). Paracetamol prompted a reduction in the activities SOD and CAT and exhibited the most pronounced toxic response when compared to the other treatments. The gene expression patterns paralleled those of oxidative stress, with all treatments demonstrating overexpression of bax, bcl2, and p53. The above suggested a probable apoptotic response in the liver of the fish. Nevertheless, our histological examinations revealed that none of the treatments induced an apoptotic or inflammatory response in the hepatocytes. Instead, the observed tissue alterations encompassed leukocyte infiltration, sinusoidal dilatation, pyknosis, fatty degeneration, diffuse congestion, and vacuolization. In summary, the hepatic toxicity elicited by COVID-19 drugs in zebrafish was less pronounced than anticipated. This attenuation could be attributed to metformin's antioxidant and hormetic effects.

Asunto(s)

Acetaminofén , Hígado , Metformina , Estrés Oxidativo , Pez Cebra , Animales , Hígado/efectos de los fármacos , Hígado/metabolismo , Estrés Oxidativo/efectos de los fármacos , Acetaminofén/toxicidad , Metformina/farmacología , Dexametasona/farmacología , COVID-19 , Apoptosis/efectos de los fármacos , Tratamiento Farmacológico de COVID-19 , Superóxido Dismutasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Catalasa/metabolismo , Contaminantes Químicos del Agua/toxicidad

RESUMEN

This study assessed the effects of dexamethasone treatment on farrowing performance and piglet traits in the first 5 days of life in multiparous sows, a high-risk group for stillbirths and prolonged farrowing. In this study, 185 multiparous sows (parity 4.25 ± 0.14) were selected on the day of farrowing and divided into three treatments: CON - control, without dexamethasone treatment; DexaPF - treatment with dexamethasone (20 mg im per female) at the time of copious colostrum secretion (pre-farrowing); and DexaFO - treatment with dexamethasone (20 mg im per female) when the first piglet was born (farrowing onset). All sows and their litters were monitored for farrowing duration, obstetric interventions, colostrum yield and intake, newborn piglet traits, and piglet performance until 5 d of age. A subsample of 106 females (∼35 per treatment) had their blood glucose concentration checked hourly shortly after the first piglet was born until the end of farrowing. Additionally, blood samples from 42 litters were collected for immunocrit evaluation. The results showed no differences regarding farrowing duration (CON = 258.02 ± 13.81 min; DexaPF = 251.29 ± 13.60 min; DexaFO = 294.92 ± 13.89 min; P = 0.06) and obstetric intervention rates among treatments (CON = 36.58 ± 6.78 %; DexaPF = 42.16 ± 6.89 %; DexaFO = 48.05 ± 7.08 %; P = 0.45). The blood glucose concentration during farrowing was higher in DexaPF (94.56 ± 1.57 mg/dL; P < 0.001) than in CON (73.50 ± 1.72 mg/dL) and DexaFO (87.94 ± 1.80 mg/dL). No differences were observed regarding total piglets born and born alive, stillborn, newborn piglet vitality, colostrum intake, immunocrit, colostrum yield, and glycemia and rectal temperature at 24 h of age (P ≥ 0.13). Regarding meconium staining, higher percentages of piglets born without meconium staining were observed in DexaFO (54.77 ± 5.21 %; P = 0.02) compared with CON (48.58 ± 5.26 %), and no difference was observed for the DexaPF group (53.23 ± 5.21 %). In addition, a higher unbroken umbilical cord rate was observed in DexaFO (92.41 ± 1.31 %; P < 0.01) than the CON or DexaPF (86.91 ± 1.97 % and 89.31 ± 1.67 %, respectively). However, the treatments did not affect piglet performance (weight gain and survival) until 5 d of age (P ≥ 0.15). In summary, dexamethasone treatment in periparturient multiparous sows did not improve farrowing performance and key production parameters, such as the piglet weight gain and survival up to 5 d of age.

Asunto(s)

Animales Recién Nacidos , Dexametasona , Animales , Femenino , Dexametasona/farmacología , Dexametasona/administración & dosificación , Porcinos/fisiología , Embarazo , Paridad , Parto/efectos de los fármacos , Periodo Periparto , Calostro/química

RESUMEN

White adipose tissue (WAT) regulates energy balance through energy storage, adipokines secretion and the thermogenesis process. Beige adipocytes are responsible for WAT thermogenesis. They are generated by adipogenesis or transdifferentiation during cold or ß3-adrenergic agonist stimulus through a process called browning. Browning has gained significant interest for to its preventive effect on obesity. Glucocorticoids (GCs) have several functions in WAT biology; however, their role in beige adipocyte generation and WAT browning is not fully understood. The aim of our study was to determine the effect of dexamethasone (DXM) on WAT thermogenesis. For this purpose, rats were treated with DXM at room temperature (RT) or cold conditions to determine different thermogenic markers. Furthermore, the effects of DXM on the adipogenic potential of beige precursors and on mature beige adipocytes were evaluated in vitro. Our results showed that DXM decreased UCP-1 mRNA and protein levels, mainly after cold exposure. In vitro studies showed that DXM decreased the expression of a beige precursor marker (Ebf2), affecting their ability to differentiate into beige adipocytes, and inhibited the thermogenic response of mature beige adipocytes (Ucp-1, Dio2 and Pgc1α gene expressions and mitochondrial respiration). Overall, our data strongly suggest that DXM can inhibit the thermogenic program of both retroperitoneal and inguinal WAT depots, an effect that could be exerted, at least partially, by inhibiting de novo cell generation and the thermogenic response in beige adipocytes.

Asunto(s)

Tejido Adiposo Pardo , Tejido Adiposo Blanco , Ratas , Animales , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Obesidad/metabolismo , Adipogénesis , Dexametasona/farmacología , Termogénesis

RESUMEN

AIM: The anaesthetic success rate of an inferior alveolar nerve block (IANB) in mandibular molars with irreversible symptomatic pulpitis can be low, and postoperative pain control in teeth with this diagnosis can be challenging. This study aimed to evaluate the influence of preemptive use of dexamethasone and oral potassium diclofenac on the success of IANB. The influence of these drugs on the intensity of postoperative pain was assessed as a secondary outcome. METHODOLOGY: Eighty-four patients with mandibular molars diagnosed with irreversible symptomatic pulpitis recorded preoperative pain intensity using a cold thermal test and a modified Numerical Rating Scale (mNRS). Sixty minutes before the anaesthetic procedure, patients were randomly assigned to one of three groups based on the medication they received: dexamethasone (4 mg), diclofenac potassium (50 mg), or placebo. All patients received IANB with 4% articaine (1:200 000 epinephrine), and 15 min later, they were evaluated for pain intensity using the cold thermal test. Anaesthetic success was analysed. The pain intensity was then recorded, and endodontic treatment and provisional restoration of the tooth were executed in a single session. Patients were monitored for 6, 12, 24, 48 and 72 h using the mNRS to assess the intensity of postoperative pain. RESULTS: There was a statistically significant increase in anaesthetic success when 4 mg dexamethasone (39.3%) or 50 mg diclofenac potassium (21.4%) was used compared to the placebo group (3.6%) (p < .001), with no significant difference between the two drugs. Regarding postoperative pain, dexamethasone was superior to placebo at 6 h (p < .001), with diclofenac having an intermediate behaviour, not differing between dexamethasone and placebo (p > .05). There was no significant difference amongst the groups at 12 h (p > .05). At 24, 48 and 72 h, the effectiveness of dexamethasone and diclofenac were comparable, and both were superior to placebo (p < .001). CONCLUSION: The use of dexamethasone or diclofenac potassium was favourable in terms of increasing the success rate of inferior alveolar nerve block in cases of mandibular molars with irreversible symptomatic pulpitis and decreased the occurrence of postoperative pain when compared to the use of a placebo.

Asunto(s)

Anestesia Dental , Anestésicos , Bloqueo Nervioso , Pulpitis , Humanos , Anestesia Dental/métodos , Anestésicos/farmacología , Anestésicos Locales , Antiinflamatorios/farmacología , Dexametasona/farmacología , Diclofenaco/farmacología , Método Doble Ciego , Lidocaína , Nervio Mandibular , Diente Molar/cirugía , Bloqueo Nervioso/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Pulpitis/cirugía

RESUMEN

The synthesized peptide derived from Enterolobium contortisiliquum (pep3-EcTI) has been associated with potent anti-inflammatory and antioxidant effects, and it may be a potential new treatment for asthma-COPD overlap-ACO). Purpose: To investigate the primary sequence effects of pep3-EcTI in an experimental ACO. BALB/c mice were divided into eight groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep3-EcTI (treated with inhibitor), ACO-DX (treated with dexamethasone), ACO-DX-pep3-EcTI (treated with dexamethasone and inhibitor), and SAL-pep3-EcTI (saline group treated with inhibitor). We evaluated the hyperresponsiveness to methacholine, exhaled nitric oxide, bronchoalveolar lavage fluid (BALF), mean linear intercept (Lm), inflammatory markers, tumor necrosis factor (TNF-α), interferon (IFN)), matrix metalloproteinases (MMPs), growth factor (TGF-ß), collagen fibers, the oxidative stress marker inducible nitric oxide synthase (iNOS), transcription factors, and the signaling pathway NF-κB in the airways (AW) and alveolar septa (AS). Statistical analysis was conducted using one-way ANOVA and t-tests, significant when p < 0.05. ACO caused alterations in the airways and alveolar septa. Compared with SAL, ACO-pep3-EcTI reversed the changes in the percentage of resistance of the respiratory system (%Rrs), the elastance of the respiratory system (%Ers), tissue resistance (%Gtis), tissue elastance (%Htis), airway resistance (%Raw), Lm, exhaled nitric oxide (ENO), lymphocytes, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, transforming growth factor (TGF)-ß, collagen fibers, and iNOS. ACO-DX reversed the changes in %Rrs, %Ers, %Gtis, %Htis, %Raw, total cells, eosinophils, neutrophils, lymphocytes, macrophages, IL-1ß, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, TGF-ß, collagen fibers, and iNOS. ACO-DX-pep3-EcTI reversed the changes, as was also observed for the pep3-EcTI and the ACO-DX-pep3-EcTI. Significance: The pep3-EcTI was revealed to be a promising strategy for the treatment of ACO, asthma, and COPD.

Asunto(s)

Asma , Enfermedad Pulmonar Obstructiva Crónica , Animales , Ratones , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Ovalbúmina/metabolismo , Interleucina-13/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Interleucina-6/metabolismo , Metaloproteinasa 12 de la Matriz/metabolismo , Asma/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Pulmón/patología , Inflamación/metabolismo , Inhibidores de Proteasas/farmacología , Líquido del Lavado Bronquioalveolar , Estrés Oxidativo , Colágeno/metabolismo , Elastasa Pancreática/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Dexametasona/farmacología , Ratones Endogámicos BALB C , Modelos Animales de Enfermedad

RESUMEN

The molecular processes that underlie long-term memory formation involve signaling pathway activation by neurotransmitter release, which induces the expression of immediate early genes, such as Zif268, having a key role in memory formation. In this work, we show that the cannabinoid CB1 receptor signaling is necessary for the effects of dexamethasone on the behavioral response in an inhibitory avoidance task, on dexamethasone-induced ERK phosphorylation, and on dexamethasone-dependent Zif268 expression. Furthermore, we provide primary evidence for the mechanism responsible for this crosstalk between cannabinoid and glucocorticoid-mediated signaling pathways, showing that dexamethasone regulates endocannabinoid metabolism by inhibiting the activity of the Fatty acid amide hydrolase (FAAH), an integral membrane enzyme that hydrolyzes endocannabinoids and related amidated signaling lipids. Our results provide novel evidence regarding the role of the endocannabinoid system, and in particular of the CB1 receptor, as a mediator of the effects of glucocorticoids on the consolidation of aversive memories.

Asunto(s)

Cannabinoides , Consolidación de la Memoria , Endocannabinoides/metabolismo , Receptor Cannabinoide CB1/genética , Cannabinoides/farmacología , Transducción de Señal , Glucocorticoides/farmacología , Dexametasona/farmacología , Amidohidrolasas , Moduladores de Receptores de Cannabinoides/farmacología

RESUMEN

The use of anti-venom is one of the main control measures for snakebite envenoming when applied immediately after the snakebite. Systemic effects of the envenoming are usually reversed; however, neutralization of local effects is hardly achieved. The need for adjuvant therapies associated with serum therapy can improve the treatment for local effects of envenoming, with greater effectiveness in preventing or delaying the progression of damage, reducing the clinical signs and symptoms of victims of snakebites. The purpose of the study was to evaluate the photobiomodulation therapy using LED and/or dexamethasone associated with conventional serum therapy for the treatment of local damage caused by Bothrops atrox envenomation in a murine model. For this, experimental envenoming was carried out in the gastrocnemius muscle of male Swiss mice weighing 18 to 22 g divided into 8 groups of animals, distributed in groups non-treat, treated with anti-bothropic serum, dexamethasone, and LED, or the associated treatments, by intramuscular inoculation of 50 µg of venom or sterile PBS (control). After 30 min, the proposed treatments were administered alone or in combination. After 3 h, blood and muscle samples were collected for myotoxicity, cytotoxicity, histological analysis, and IL-1ß assays. The evaluation of the treatment alone showed that serum therapy is not effective for the treatment of local damage and photobiomodulation demonstrated to be an effective therapy to reduce leukocyte infiltration, hemorrhage, and myotoxicity in experimental envenoming; dexamethasone proved to be a good resource for the treatment of the inflammatory process reducing the leukocyte infiltration. The association of serum therapy, LED, and dexamethasone was the best treatment to reduce the local effects caused by Bothrops atrox venom. All in all, the association of photobiomodulation therapy using LED with conventional serum therapy and the anti-inflammatory drug is the best treatment for reducing the undesirable local effects caused by snakebite accidents involving B. atrox species.

Asunto(s)

Bothrops , Venenos de Crotálidos , Mordeduras de Serpientes , Masculino , Animales , Ratones , Mordeduras de Serpientes/tratamiento farmacológico , Miotoxicidad/patología , Músculo Esquelético/patología , Dexametasona/farmacología , Dexametasona/uso terapéutico

RESUMEN

BACKGROUND: Severe cases of Coronavirus Disease 2019 (COVID-19) that require admission to the Intensive Care Unit (ICU) and mechanical ventilation assistance show a high mortality rate with currently few therapeutic options available. Severe COVID-19 is characterized by a systemic inflammatory condition, also called "cytokine storm", which can lead to various multi-organ complications and ultimately death. Lidocaine, a safe local anesthetic that given intravenously is used to treat arrhythmias, has long been reported to have an anti-inflammatory and pro-homeostatic activity. METHODS: We studied the capacity of lidocaine to modulate cytokine secretion of mouse and human myeloid cell lines activated by different cytokines or Toll Like Receptor (TLR) ligands (flagellin (FliC), Lipopolysaccharide (LPS), Polyinosinic:polycytidylic acid (Poly I:C) and N-Palmitoyl-S- [2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine x 3HCl (Pam3Cys-SKKKK)) or by Severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) infection to epithelial cells. Reporter cell lines were used to study modulation of lidocaine of specific signaling pathways. RESULTS: Lidocaine used in combination with dexamethasone, had an additive effect in the modulation of cellular inflammatory response triggered by Tumoral Necrosis Factor alpha (TNFα), Interleukin 1 beta (IL-1ß) as well as different TLR ligands. We also found that lidocaine in combination with dexamethasone modulates the Nuclear factor kappa B (NF-κB) pathway, inflammasome activation as well as interferon gamma receptor (IFNγR) signaling without affecting the type I interferons (Type I IFNs) pathway. Furthermore, we showed that lidocaine and dexamethasone treatment of epithelial cells infected with SARS-CoV-2 modulated the expression of chemokines that contribute to pro-inflammatory effects in severe COVID. CONCLUSIONS: We reported for the first time in vitro anti-inflammatory capacity of lidocaine on SARS-CoV-2 triggered immune pathways. These results indicated the potential of lidocaine to treat COVID-19 patients and add tools to the therapeutic options available for these concerning cases.

Asunto(s)

COVID-19 , Citocinas , Humanos , Citocinas/metabolismo , SARS-CoV-2 , Lidocaína/farmacología , Tratamiento Farmacológico de COVID-19 , Antiinflamatorios/farmacología , Células Epiteliales/metabolismo , Receptores Toll-Like , Dexametasona/farmacología

RESUMEN

Research on host response to infectious disease often involves pharmacological induction of immunosuppression, frequently through administration of dexamethasone. Reports on the effect of dexamethasone in birds are largely restricted to poultry and pigeons. This study describes changes in white blood cell (WBC) differentials, hemoparasite counts, splenic histology, and splenic CD3 immunoreactivity in House Finches (Haemorhous mexicanus). Experimental group birds (n=9) were treated with a daily intramuscular injection of 25 µg of dexamethasone for 8 d; a control group (n=9) received daily saline solution. Smears were made with blood collected immediately before the first dose (day 0) and on d 4, 8, and 9, and stained with modified Wright. The WBC differential counts were performed by three blinded observers, parasite counts by two blinded observers, and histology by one blinded observer. Dexamethasone-treated birds experienced relative heterophilia and lymphopenia on d 4 (P=0.008); heterophilia was also present at d 8 (P=0.018). Hemosporidian counts were significantly increased in dexamethasone-treated birds on d 4 and 8 (P=0.048 and P=0.031, respectively). In contrast with control birds, all dexamethasone-treated birds lacked histologically apparent splenic lymphoid follicles (P<0.001). No significant difference was observed in splenic CD3 immunoreactivity between groups. Our results indicate that dexamethasone has an effect on the hematologic profile of House Finches and suggest that it may be a useful method to induce immunosuppression in this species.

Asunto(s)

Enfermedades de las Aves , Pinzones , Infecciones por Mycoplasma , Animales , Enfermedades de las Aves/tratamiento farmacológico , Dexametasona/farmacología , Pinzones/fisiología , Infecciones por Mycoplasma/veterinaria

RESUMEN

Objective: The present study investigated the antifungal action of dexamethasone disodium phosphate (Dex). Methodology: Susceptibility testing was performed using the Clinical & Laboratory Standards Institute protocol; M27-A3, checkerboard test and biofilm were evaluated with two isolates of Candida albicans, hyphal production test, molecular docking analysis and flow cytometry analysis. Result: Dex and fluconazole (FLC) together had a synergistic effect. Mature biofilm was reduced when treated with Dex alone or in combination. Dex and FLC promoted a decrease in the production of hyphae and changes in the level of mitochondrial depolarization, increased generation of reactive oxygen species, loss of membrane integrity, increased phosphatidylserine externalization and molecular docking; there was interaction with ALS3 and SAP5 targets. Conclusion: Dex showed antifungal activity against FLC-resistant C. albicans strains.

---

This study aimed to evaluate the antifungal action of dexamethasone against FLC-resistant C. albicans strains.

Asunto(s)

Candida albicans , Fluconazol , Antifúngicos/farmacología , Biopelículas , Dexametasona/farmacología , Farmacorresistencia Fúngica , Sinergismo Farmacológico , Fluconazol/farmacología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular

RESUMEN

Dexamethasone (Dexa) is a potent glucocorticoid that can trigger side effects, such as neuromuscular, cardiovascular, and gastric motility disorders. Exercise can ameliorate gastrointestinal disorders. However, it is not clear whether exercise can modulate the side effects of using Dexa on gastric motility. To investigate the role of anaerobic resistance training (ART) on gastric motility and feeding behavior of rats treated with dexamethasone, rats were divided into three groups: control (Ctrl), dexamethasone (Dexa), and anaerobic resistance training + dexamethasone (ARTDexa). Anaerobic resistance training (ART) consisted of climbing a vertical ladder 5 days/week (with intensity of 50% to 100% of the maximum overload/8 weeks). At the end of the ART or control period, the rats received Dexa (1 mg/kg i.p) for 10 consecutive days. In the end, we evaluated anthropometric parameters and feeding behavior, heart rate, gastric emptying, and lipid profile in all groups. We observed significant decrease (p < 0.05) in body weight and food intake in the Dexa and ARTDexa groups compared to the control. Dexa promoted significant tachycardia (p < 0.05) and a decrease (p < 0.05) in the r-r' interval. The ART significantly prevented (p < 0.05) cardiovascular effects. Dexa induced a decrease (p < 0.05) in gastric emptying compared to the control group. On the other hand, ART significantly prevented (p < 0.05) the decrease in gastric emptying compared to Dexa. The chronic use of Dexa caused tachycardia, decreased food intake, and decreased gastric emptying. The ART modulated cardiovascular parameters, improving tachycardia. In addition, this exercise prevented gastric dysmotility induced by dexamethasone.

Asunto(s)

Vaciamiento Gástrico , Entrenamiento de Fuerza , Anaerobiosis , Animales , Dexametasona/farmacología , Vaciamiento Gástrico/fisiología , Humanos , Ratas , Ratas Wistar